Lithium regulation of aldolase A expression in the rat frontal cortex: Identification by differential display

Background: Substantial evidence indicates that lithium may exert its thera peutic effects through progressive adaptive changes at the level of gene ex pression; however, the study of lithium-regulated genes has been primarily undertaken with the "candidate gene" approach based on a specific testable hypothesis. The aim of our study was to identify lithium-regulated genes th at would not be predicted a priori by the candidate gene approach. Methods: Differential display polymerase chain reaction was used to isolate and identify messenger RNAs (mRNAs) that ar-e differentially expressed in the frontal cortex of rats given lithium for 5 weeks to achieve plasma lith ium concentrations of 0.6 to 0.9 mmol/L. Results: A putative lithium-regulated complementary DNA fragment (LRG1) was identified. Northern blot analysis revealed that 5 weeks of lithium treatm ent but not I week, significantly reduced LRG1 mRNA levels. LRG1 mRNA level s were similarly reduced by 5 weeks of carbamazepine, but not valproate adm inistration. Sequence analysis and search of the GenBank database revealed that LRG1 is analogous to the sequence of the gene for rat aldolase A. Conclusions: These results demonstrate that chronic administration of lithi um, but not short-term administration, downregulates the levels of aldolase A mRNA, suggesting this effect may play a role in mediating the therapeuti c action of this agent. (C) 2000 Society of Biological Psychiatry.